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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
Test method was not according to any guideline. The species used was the rabbit. However, the recommended species for the acute inhalation toxicity is the rat. No GLP.

Data source

Reference
Reference Type:
publication
Title:
Nutmeg Oil and Camphene as Inhaled Expectorants
Author:
Boyd EM
Year:
1970
Bibliographic source:
Arch Otolaryng., Vol. 92, pp. 372-378.

Materials and methods

Principles of method if other than guideline:
- Principle of test: Studies on the pharmacological expectorant activity of nutmeg oil and camphene given by inhalation to rabbits arranged for the collection of respiratory tract fluid.
- Short description of test conditions: see below
- Parameters analysed / observed: volumen of respiratory tract fluid, expectorant activity and odor
GLP compliance:
no
Test type:
other: Study of the pharmacological expectorant activity of test substance
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young
- Weight at study initiation: 2-3 kg
- Housing: They were housed in boarding cages, one animal per cage.
- Diet (e.g. ad libitum): They were fed a standard rabbit ration of mixed natural foods, salts, and vitamins.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
other: ethanol
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
In preparation for the collection of respiratory tract fluid, the rabbits were anesthetized with urethane (ethyl carbamate) given by intraperitoneal injection in a dose of 4.0 to 5.0 mL/kg body weight of a 25% (w/v) solution in distilled water. This produced a light anesthesia lasting over 24 hours with no reported effect on the volume and composition of respiratory tract fluid except that it augmented the concentration of potassium ion.
One arm of a T-shaped cannula was ligated into the trachea, a collecting tube attached to the second arm, and the third arm was connected with a reservoir of conditioned air maintained at 39 ºC and saturated with water vapor. The conditioned air was prepared by mixing laboratory air with steam from a thermostatically controlled water vaporizer. Steam generated by this vaporizer volatilized the test item which was carried to the conditioned air reservoir from which it was inhaled by each anesthetized rabbit.
Respiratory tract fluid was collected for a control period of two to four hours. The collecting tube was then replaced by a cleaned, empty tube, test item added to the vaporizer, and respiratory tract fluid collected for a subsequent period of four to six hours.


Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
>= 4 - <= 6 h
Concentrations:
1, 3, 9, 27, 81, and 243 mg/kg
No. of animals per sex per dose:
4-6 male rabbits per dose
Control animals:
other: The controls were the same animals, before being treated.
Details on study design:
- Duration of observation period following administration: 24 hours, which is a standard method of expressing the volume output of respiratory tract fluid.

Results and discussion

Effect levels
Key result
Sex:
male
Dose descriptor:
LC0
Effect level:
>= 243 other: mg/kg
Based on:
test mat.
Exp. duration:
6 h
Mortality:
No animals died during the study.
Clinical signs:
Inhalation of camphene by urethanized rabbits in doses 3-27 mg/kg produced significant increase in volume output of respiratory tract fluid, accompanied by decrease in specific gravity and increase in total solids. Dose-dependent increase in volume output of respiratory tract fluid varied with the season. The expectorant action began to disappear following inhalation of a dose of 81 mg/kg, which is well below the level detectable by odour (243 mg/kg) and far below the probably fatal dose.

Any other information on results incl. tables

The LC 0 was equal or greater than 243 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
The LC 0 was equal or greater than 243 mg/kg.
Executive summary:

Camphene was given by inhalation to male rabbits that were anesthetized with urethane (ethyl carbamate) for 24 hours and were arranged for collection of respiratory tract fluid. Test substance was dissolved in 1 mL of ethanol in amounts of 1, 3, 9, 27, 81, and 243 mg. Each dose was given to 4 to 6 rabbits. Respiratory tract fluid was collected for a control period of two to four hours. The collecting tube was then replaced by a cleaned, empty tube, test item added to the vaporizer, and respiratory tract fluid collected for a subsequent period of four to six hours. Steam generated by the water vaporizer volatilized the test item which was carried to the conditioned air reservoir from which it was inhaled by each anesthetized rabbit. Inhalation of camphene by urethanized rabbits in doses 3-27 mg/kg produced significant increase in volume output of respiratory tract fluid, accompanied by decrease in specific gravity and increase in total solids. Dose-dependent increase in volume output of respiratory tract fluid varied with the season. The expectorant action began to disappear following inhalation of a dose of 81 mg/kg, which is well below the level detectable by odour (243 mg/kg) and far below the probably fatal dose. Based on these results, the LC0 was established to be equal or greater than 243 mg/kg.